3/23/2017
Debating Electronic Nicotine Delivery
Systems: Harms and Benefits
Robin Corelli, PharmD
UCSF School of Pharmacy
Karen Hudmon, DrPH, MS, RPh
Purdue University College of Pharmacy
Disclosures
Drs. Corelli and Hudmon declares no conflicts of interest, real or apparent, and
no financial interests in any company, product, or service mentioned in this
program, including grants, employment, gifts, stock holdings, and honoraria.
.
•
Target Audience: Pharmacists and Pharmacy Technicians
•
ACPE#: 0202-0000-17-064-L04-P
•
Activity Type: Knowledge-based
The American Pharmacists Association is accredited by the
Accreditation Council for Pharmacy Education as a provider
of continuing pharmacy education.
Learning Objectives
Assessment Question #1
1. Discuss potential benefits of ENDS as a harm-reduction strategy
for current smokers.
Which of the following is an established benefit of ENDS
use in current smokers:
2. Describe the individual risks associated with the use of ENDS.
A. Reduced exposure to toxins present in tobacco smoke
3. Describe the population-level risks associated with the use of
ENDS.
B. Reduced risk associated with second-hand exposure to water
vapor
4. Formulate an opinion regarding the role of ENDS as a tobacco
control strategy.
C. Increased odds of quitting completely
D. Reduced dependence on nicotine
1
3/23/2017
Assessment Question #2
Which of the following negative consequences have been
reported with use of ENDS?
Assessment Question #3
Which of the following statements is true?
A. Use of ENDS is an effective treatment for smoking cessation.
B. Among US adults, use of ENDS occurs predominantly among
former smokers.
A. Burns
B. Oral leukoplakia
C. Peripheral neuropathy
D. A and B
C. ENDS products have similar levels of carcinogens as
combustible tobacco products.
D. Among US high school students, the use of ENDS has been
shown to be associated with progression to cigarette
smoking.
Based on current evidence, health-care providers
should recommend the use of ENDS for smoking
cessation:
The content for this session derives from the
Rx for Change: Clinician-Assisted Tobacco Cessation program.
Strongly agree
Agree
Disagree
Strongly disagree
Copyright © 1999-2017 The Regents of the University of California.
All rights reserved.
http://rxforchange.ucsf.edu
Electronic Nicotine Delivery Systems (ENDS):
Background
•
Devices similar in appearance to
cigarettes, cigars, pipes, or pens
•
Battery-operated devices that create a
vapor for inhalation
– Simulates smoking but does not involve combustion
of tobacco
•
Also known as:
– E-cigarette
– E-hookah, Hookah pen
– Vapes, Vape pen, Vape pipe
– Electronic nicotine delivery system (ENDS)
Image from: http://www.nytimes.com/2014/03/05/business/e-cigarettes-under-aliases-elude-the-authorities.html
2
3/23/2017
ENDS: Device Variability
Product
Characteristics
Disposable
Cigarette-shaped;
battery + cartridge with atomizer; not
rechargeable
Rechargeable
Cigarette-shaped; rechargeable battery
connects to atomizer; often contains
element to regulate inhalations
Pen-style
Larger device, often with higher capacity
battery; refillable cartridge; manual
switch to regulate inhalations
Tank-style
Much larger; higher capacity battery;
large refillable cartridge; easily modified
E-liquid Constituents
• Solutions generally contain:
– Propylene glycol (PG)
– Vegetable glycerin (VG)
– Flavorings (>7,000 available)
– Nicotine (0-36 mg/mL)
Images from Grana et al., https://escholarship.org/uc/item/13p2b72n
To Vape or Not to Vape
• Intensely debated topic / public health community divided
– USA versus British position on ENDS
• What are the public health implications of broad-scale
acceptance of ENDS?
• What do clinicians need to know when treating patients?
– Are ENDS effective for smoking cessation?
– Are ENDS safe?
Differing Views on ENDS
“Disruptive technology” that will end smoking
“Huge gains for public health if all smokers adopt ENDS use”
— versus —
“A distraction from the tobacco end-game”
“A major threat to tobacco control…will discourage quitting,
renormalize smoking, recruit new cigarette smokers, and
further strengthen Big Tobacco”
Professor Christopher Bullen, University of Auckland
U.S. Position
“The current evidence is insufficient to recommend
electronic nicotine delivery systems (ENDS) for
tobacco cessation.”
“Clinicians should direct patients who smoke tobacco
to other cessation interventions with established
effectiveness and safety.”
Tobacco Smoking Cessation in Adults, Including Pregnant Women: Behavioral and Pharmacotherapy
Interventions.
U S Preventive Services Task Force September 2015
Professional Organizations/Associations
with Policies & Position Statements on ENDS
•
•
•
•
•
•
•
•
•
•
•
•
American Pharmacists Association
American Medical Association
American College of Physicians
American Heart Association
American Cancer Society
US National Association of County and City Health Officials
American Diabetes Association
American Association for Cancer Research
American Society of Clinical Oncology
American Academy of Pediatrics
California Department of Public Health
Forum of International Respiratory Societies
3
3/23/2017
Public Health Implications of
Broad-scale Acceptance of ENDS
British Position
“Smokers who have tried other methods of quitting without success could
be encouraged to try e-cigarettes to stop smoking.”
“Encouraging smokers who cannot or do not want to stop smoking to
switch to e-cigarettes could help reduce smoking-related disease, death,
and health inequalities.”
“There is no evidence that e-cigarettes are undermining the long-term
decline in cigarette smoking among adults and youth, and may in fact be
contributing to it.”
Key issues for debate:
Among adults:
• Dual use of tobacco and ENDS
• Recidivism to nicotine dependence among former smokers
Among youth and young adults:
• Onset of ENDS use versus onset of tobacco smoking
• Transition from ENDS use to tobacco use
McNeill et al. E-cigarettes: An evidence update. A report commissioned by Public Health England, 2015.
Current E-Cigarette Use* by Age
and Smoking Status—U.S. Adults, 2015
Past-Month E-Cigarette and Cigarette Use
Among U.S. Middle and High School Students, 2015*
Current cigarette smokers
Former cigarette smokers
Never cigarette smokers
Percent of e-cigarette users
90
80
70
60
50
40
30
20
In 2015,
3.5% of
adults
were
current
ENDS
users
Percent
*Respondents who reported every day or some day e-cigarette use
100
20
18
16
14
12
10
8
6
4
2
0
Cigarette use in past 30 days
E-cigarette use in past 30 days
16.2
Between 2013 and
2014, current use of
e-cigarettes tripled
and surpassed the
current use of
cigarettes.**
14.0
9.5
4.9
6.1
3.2
8th grade
10th grade
12th grade
10
0
18-24 years
25-44 years
45+ years
Total
Cigarette Smoking Status Among Current Adult E-cigarette Users, by Age Group —
National Health Interview Survey, United States, 2015. MMWR Morb Mortal Wkly Rep 2016;65:1177.
*Johnston et al. (2016). Monitoring the Future national survey results on drug use, 1975-2015.
Overview, key findings on adolescent drug use. Ann Arbor: Institute for Social Research, The University of Michigan.
**Centers for Disease Control and Prevention (2015). MMWR 64:381–385.
Conversion from E-Cigarette Use to Tobacco
Smoking in Early Adolescence
• National survey: ENDS use  increased intention to smoke cigarettes1
– 43.9% among ever users vs 21.5% among never users (p<0.001)
• High school students who report ENDS use are more likely than non-
users to initiate tobacco smoking in the following 12 months2
– More frequent ENDS use is associated with higher risk for more frequent,
heavy smoking 6 months later3
– ENDS use is not associated with smoking reductions among current
smokers3
1Bunnell
et al., Nicotine Tob Res 2015;17:228–235.
et al., JAMA 2015;314:700–707.
et al., JAMA 2016;316:1918–1920.
2Leventhal
3Leventhal
4
3/23/2017
What Does the Evidence Suggest?
• Among adults, use of ENDS occurs predominantly among
current smokers; data suggest recidivism among former
smokers
• Among adolescents and young adults, current use now
exceeds tobacco use
• Evidence suggests that ENDS use leads to cigarette
smoking among high school students
Public Health Implications:
Broadscale Acceptance of ENDS
Positive if:
Negative if:
• ENDS are safe
• ENDS are harmful
• All current smokers switch to
ENDS (harm reduction)
• Smoking is “renormalized”
• All current smokers quit
smoking; no dual use
• Smokers completely switch to
ENDS as a step toward
complete cessation
• Ongoing, prospective monitoring is warranted
What Clinicians Need to Know Regarding
the Efficacy of ENDS for Smoking Cessation
• Reduced quitting due to dual
use (smoking + ENDS)
• Recidivism among former
smokers
Randomized Trial of Smoking Cessation
In patients who are motivated to quit, are ENDS efficacious
for smoking cessation?
Key issues for debate:
• ENDS as a viable and acceptable treatment option for
smokers
• Efficacy of ENDS for use in smoking cessation
Characteristic
Randomized Trial: 6-Month Results
Results: Continuous Abstinence
Nicotine e-cigarette vs Nicotine transdermal patch
16 mg e-cigarette
(n=289)
21mg nicotine
patch (n=295)
Placebo e-cigarette
(n=73)
21 (7.3%)
17 (5.8%)
3 (4.1%)
No significant differences
Bullen et al., 2013
Study population
Motivated to Quit
Sample size
657
Intervention arms
16 mg e-cig
21 mg nicotine patch
0 mg e-cig
• Comparison of ENDS versus cessation medications
6 months
• ENDS use leads to tobacco
smoking (e.g., gateway)
Behavioral support
Minimal
Period of intervention
13 weeks
Duration of follow-up
6 months
Primary outcome
Continuous abstinence at 6 mo, verified by expired CO
Randomized Trial: Results (cont’d)
• ENDS can reduce the desire to smoke and reduce nicotine
withdrawal symptoms
• As a result of using ENDS, some smokers reduce the number
of cigarettes smoked or quit smoking
• Side effects:
– No serious events reported
– No significant differences between nicotine patch and ENDS
Bullen et al., Lancet 2013;382:1629–1637.
5
3/23/2017
Strengths
Limitations
Early trial; first-generation (unreliable) ENDS formulation
now antiquated
In comparison group, low adherence with nicotine patch
•
Large trial (n=657)
•
•
Randomized design, with comparison groups
•
•
6-month follow-up period
•
•
Verified continuous abstinence outcome at 6 months
Differential methods for receiving patch versus ENDS
products
•
High loss to follow-up; higher in patch vs ENDS group
•
Little behavioral support
Underpowered
•
Relationship Between ENDS Use and Quitting
Smoking: Real-world and Clinical Settings
30
Long-term (≥6 month) Quit Rates for
Available
First-line Cessation Medications
Bullen (2013)
Active drug
Vickerman (2013)
25
25.6
23.9
Placebo
Borderud (2014)
Percent quit
Hajek (2015)
Pavlov (2015)
OVERALL
-1.00
-0.50
16.3
17.1
15.9
15
11.8
10.0
10
Pearson (2015)
19.7
18.9
20
Brown (2014)
9.8
8.4
11.5
11.1
9.1
5
0.00
0.50
1.00
1.50
2.00
2.50
Odds Ratio
Does not favor ENDS
Favors ENDS
Kalkhoran & Glantz. Lancet Respir Med 2016;4:116–128.
What Does the Evidence Suggest?
• Tobacco remains the #1 preventable cause of disease and
death in the US
– First-line treatment options are inadequate
– Alternative approaches are needed // potential role for ENDS?
• The efficacy of ENDS as an aid for sustained smoking
cessation has not been established
• Data from one randomized trial suggest that ENDS are not
superior to the nicotine patch for cessation
0
Nicotine gum
Nicotine patch
Nicotine lozenge Nicotine nasal spray
Nicotine inhaler
Bupropion
Varenicline
Data adapted from Cahill et al. (2016). Cochrane Database Syst Rev;
Stead et al. (2012). Cochrane Database Syst Rev; Hughes et al. (2014). Cochrane Database Syst Rev
What Clinicians Need to Know
Regarding the Safety of ENDS
Key issues for debate:
• Health risks associated with constituents in ENDS aerosols
– Short-term effects
– Chronic effects
– Second- and third-hand exposures (data not shown)
• Toxicity associated with exposure to e-liquid
• Adverse effects caused by device malfunction
6
3/23/2017
ENDS Clinical Trials: Adverse Events
• No serious adverse events (AEs) related to ENDS use observed in RCTs
• Caponnetto (2013)
– Duration of exposure: 12 weeks
ENDS Aerosols: Potential Health Risks
Propylene Glycol (PG) and Vegetable Glycerin (VG)
• Common ingredients for producing vapor and “throat hit” sensation
• The FDA has classified both agents as “generally recognized as safe” for
oral intake
– Assessed dry cough, mouth irritation, SOB, throat irritation and headache
– No differences in frequency of AEs between groups
• Limited studies of PG exposure suggest adverse effects on airways
– Significant reduction in frequency of adverse effects over time
– Short-term exposures (e.g., aviation training, entertainment industry) have been
associated with ocular and upper airway irritation1,2
• Bullen (2013)
– Duration of exposure: 13 weeks
– Long-term indoor air exposure might exacerbate and/or induce asthma and rhinitis
in children3
– No serious adverse events, in any group, were related to product use
– ENDS AEs not significantly different from nicotine patch (RR, 1.05; 95% CI: 0.82-1.34)
Short-term use of 1st-generation ENDS appears to be well-tolerated
Health effects of long-term, frequent pulmonary inhalation are unknown
1 Wieslander
1 Caponnetto
et al., PLoS One 2013;8:e66317.
2 Bullen et al., Lancet 2013;382:1629–1637.
• Nicotine is highly addictive
• Nicotine may cause adverse cardiovascular effects (increased HR, BP),
may impair endothelial function, and accelerate atherogenesis1
– ENDS aerosols likely incur substantially lower risk when compared to smoking
•
Accidental poisoning, especially in children
– ENDS liquids typically contain 6-36 mg nicotine per mL
• Lethal adult oral dose, 40-60 mg; in children, 6 mg might be life-threatening
E-cigarette & Liquid Nicotine Exposures Reported
to U.S. Poison Centers, 2011–2016
Number of exposures reported
ENDS Aerosols:
Potential Health Risks of Nicotine
4000
3,783
3,073
3000
2000
1000
0
2011
•
•
In 2014: 466 distinct brands of ENDS and more than 7,764 unique flavors1
Flavors deemed by the Flavor & Extract Manufacturers Association (FEMA)
“generally recognized as safe” for oral use cannot be deemed safe for
inhalation2
Diacetyl or acetyl propionyl (impart buttery/fruity/cocoa flavor) found in ~75%
of sweet-flavored e-cigarette liquids—many samples exceeded NIOSH
safety limits3,4
Diacetyl, while deemed safe for ingestion by FEMA and FDA, has been
shown to cause bronchiolitis obliterans (“pop-corn lung”) when inhaled
1 Zhu
et al., Tob Control 2014;23(Suppl 3):iii3–iii9.
et al., Tob Control 2016; 25:e10–e15.
et al., Nicotine Tob Res 2015;17:168–174.
4 Allen et al., Environ Health Perspect 2016; DOI:10.1289
2 Tierney
3 Farsalinos
2012
2013
2014
2015
2016
Source: American Association of Poison Control Centers
https://aapcc.s3.amazonaws.com/files/library/E-cig__Nicotine_Web_Data_through_12.2016.pdf
& Burbank, Trends Cardiovasc Med 2016;26:515–523.
of Poison Control Centers, 2016.
ENDS: Potential Health Risks
Carcinogens1
ENDS Aerosols: Potential Health Risks
Flavoring Agents
•
460
271
2 American Association
•
1,492
1,543
– From 2012 to 2014, calls to U.S. Poison Control Centers for e-cigarette liquid
exposures increased 733% 2
1 Benowitz
et al., Occup Environ Med 2001;58:649–655.
Tob Control 2014;23:ii36–ii40.
3 Choi et al., PLoS ONE 2010;5:e13423.
2 Callahan-Lyon,
Toxin
Cigarette
E-cigarette
Ratio
(mcg/mainstream smoke)
(mcg/15 puffs)
(cig: ENDS)
Formaldehyde
1.6 – 52
0.2 – 5.6
9
Acetaldehyde
52 – 140
0.11 – 1.36
450
Acrolein
2.4 – 62
0.07 – 4.19
15
Toluene
8.3 – 70
0.02 – 0.63
120
0.005 – 0.19
0.00008 – 0.00043
380
N-Nitrosonornicotine
No safe level of exposure has been determined; with intense heating (tank models),
concentrations of formaldehyde and acetaldehyde approach those contained in tobacco
smoke2
1 Goniewicz et al., Tob Control 2014;23:133–139.
2 Kosmider
et al., Nicotine Tob Res 2014;16:1319–1326.
7
3/23/2017
Adverse effects caused by device malfunction
What Does the Evidence Suggest?
•
Data from RCTs suggests ENDS are well-tolerated during short-term
use
•
Quality control for many products is lacking; consumers do not have
reliable product information
•
Adverse health effects associated with second-hand vapor exposure
cannot be excluded
•
Nicotine in ENDS solutions increases the risk of accidental poisoning
•
Carcinogenic substances are present in some aerosols
•
Battery safety concerns (e.g., overheating, fires, explosions), primarily
with tank-models, pose additional health risks
Health effects of long-term, regular use are unknown
Key Points
Key Points
Recommendations for Clinicians
(cont’d)
Recommendations for Clinicians
•
Assess ENDS use along with tobacco use during clinical
encounters
•
Actively discourage ENDS use in current non-smokers
•
Until more is known about the potential risks, ENDS should not be
promoted as a safe alternative to smoking
•
ENDS are unproved as effective cessation aids
– Until long-term efficacy data are available, clinicians should recommend
evidence-based, FDA-approved treatments for smoking cessation
Contact Information
Robin Corelli, PharmD
UCSF School of Pharmacy
[email protected]
Karen Hudmon, DrPH, MS, RPh
Purdue University College of Pharmacy
[email protected]
•
Evidence suggests that ENDS use is safer than smoking
•
ENDS might have a role in patients who are unable to quit
smoking using proven medications and behavioral approaches
− Weigh risks and benefits on a case-by-case basis
− ENDS are currently unregulated; most contain low toxic constituents
(in lower concentrations compared to tobacco smoke)
− Advise patients to quit smoking entirely—even low levels of smoking
impose significant health risks
Assessment Question #1
Which of the following is an established benefit of ENDS
use in current smokers:
A. Reduced exposure to toxins present in tobacco smoke
B. Reduced risk associated with second-hand exposure to water
vapor
C. Increased odds of quitting completely
D. Reduced dependence on nicotine
8
3/23/2017
Assessment Question #2
Which of the following negative consequences have been
reported with use of ENDS?
Assessment Question #3
Which of the following statements is true?
A. Use of ENDS is an effective treatment for smoking cessation.
B. Among US adults, use of ENDS occurs predominantly among
former smokers.
A. Burns
B. Oral leukoplakia
C. Peripheral neuropathy
D. A and B
C. ENDS products have similar levels of carcinogens as
combustible tobacco products.
D. Among US high school students, the use of ENDS has
been shown to be associated with progression to
cigarette smoking.
Based on current evidence, health-care providers
should recommend the use of ENDS for smoking
cessation:
Strongly agree
Agree
Disagree
Strongly disagree
9